High-dose treatment of cathepsin B-activatable doxorubicin prodrug nanoparticles that induce tumor-specific immunogenic cell death for immunotherapy of melanoma with minimal systemic toxicity - PubMed
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- #melanoma
- #nanoparticles
- #chemo-immunotherapy
- High-dose cathepsin B-activatable doxorubicin prodrug nanoparticles (CatB-NPs) developed for melanoma immunotherapy.
- CatB-NPs induce tumor-specific immunogenic cell death (ICD) with minimal systemic toxicity.
- Prodrug synthesized by conjugating cathepsin B-cleavable peptide (FRRL) to doxorubicin (DOX), forming stable nanoparticles.
- CatB-NPs selectively activated in melanoma cells overexpressing cathepsin B, sparing normal and immune cells.
- Enhanced phagocytic activity of macrophages and dendritic cell (DC) maturation observed with CatB-NPs.
- Combination therapy with CatB-NPs and anti-PD-L1 antibody led to complete tumor regression in 50% of mice.
- High-dose CatB-NPs with anti-PD-L1 suppressed lung metastasis without systemic toxicity.